DRAFT June 17, 2002

Limited data on the biological effectiveness of low-energy Auger electrons are
summarized by the ICRP (1991). When an Auger-emitting radionuclide penetrates a cell but is
not incorporated into DNA, estimated RBEs for a number of endpoints, including cell killing, are
in the range of 1.5-8. These RBEs are similar to estimates for low-energy beta particles emitted
in 5H decay discussed previously. When Auger emitters, such as "I, are incorporated into DNA,
RBEs in the range of 20-40 have been estimated for such endpoints as cell transformation. These
high RBEs are supported by calculated patterns of energy deposition.

When information on whether an Auger-emitting radionuclide is incorporated into DNA
of an exposed individual is lacking, we believe that Auger electrons should be treated in the same
way as other low-energy electrons. Thus, for example, when the energy of Auger electrons is
less than 15 keV, the probability distribution of REF, that applies to low-energy beta particles
emitted in decay of *H should be used. When Auger electrons are important compared with other
low-energy electrons, their energies are nearly always less than 15 keV (Kocher, 1981).

When an Auger-emitting radionuclide is known to be incorporated into DNA, however,
we do not believe that a credible probability distribution of REF, can be developed based on
available information. Although REF, in such cases should be substantially higher than the
REF, that applies to H beta particles, there are potentially important uncertainties including, for
example, the fraction of the activity that is incorporated into DNA, the dependence of RBE on
the energy of Auger electrons, and the dependence of RBE on dose when cell killing could occur.
Thus, we support the recommendation of the ICRP (1991) and the NCRP (1993) that the
biological effectiveness of Auger emitters that are incorporated into DNA should be handled as
special cases using techniques of microdosimetry.

Summary

The biological effectiveness of low-energy electrons relative to high-energy gamma rays
is assumed to be independent of dose and dose rate under similar conditions of exposure to the
two radiations. Cancer risks in humans from exposure to electrons (e) are estimated using the
following equations:

Solid tumors (any dose and dose rate) —

R, = REF, x 2 x p (14)
‘ i DDREF, —¢
Leukemias (acute exposure) —
HR, = a(REF,, x D,) + b(REF,, x DY (15)

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DRAFT June 17, 2002

Summary

The biological effectiveness of lower-energy photons relative to high-energy gamma
rays is assumed to be independent of dose and dose rate under similar conditions of exposure to
the two radiations. Cancer risks in humans from exposure to photons (y) are estimated using the
following equations:

Solid tumors (any dose and dose rate) —

R
= YH
&, = REF, x AF, x 5 x D, ql)
Y

Leukemias (acute exposure) —

&, = a(REF,, x AF, x D,) + b(REF,, x AP, x D,) (12)

Leukemias (chronic exposure) —

wt, = a x REF, x D

, 13)

Y

where REF,, is the radiation effectiveness factor at low doses and low dose rates that applies at
photon energies of 30-250 keV, AF, is an adjustment factor representing an increase in biological
effectiveness at photon energies less than 30 keV, R,,, is the risk coefficient (ERR per Gy) at
high acute doses of high-energy gamma rays for the solid tumor of concern, a and b are the
coefficients of the linear and quadratic terms in the linear-quadratic dose-response relationship
for leukemias at high acute doses of high-energy gamma rays, DDREF, is the dose and dose-rate
effectiveness factor for gamma rays and other low-LET radiations, and D, is the absorbed dose of
photons in the organ or tissue of concern. The value of REF, for ali photons of energy greater
than 250 keV is assumed to be unity. The probability distribution of REF, at a given photon
energy is applied to all cancers.

A single probability distribution of DDREF, is applied in estimating risks of solid tumors
under conditions of chronic exposure. Under conditions of acute exposure, DDREF, depends on
the magnitude of the dose. At acute doses greater than 0.2 Gy, DDREF, is assumed to be unity.
At acute doses less than 0.2 Gy, a DDREF, that can exceed unity is applied, and the distribution
of possible values approaches the probability distribution of DDREF, under conditions of chronic
exposure as the dose approaches zero (Land et al., 2002).

The assumed probability distributions of REF, for photons of different energies are
summarized in Table 12.

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DRAFT June 17, 2002

Table 16. Estimates of RBE of tritium beta particles for
developmental and related effects’ .

Radiation and

Effect conditions RBE Reference
Mouse embryo, two-cell HTO and chronic gamma rays 1.7 Yamada et al.
to blastocyte in vitro (1982)
Teratogenic effects in rat_ HTO and chronic gamma rays 2.6 Satow et al. (1989)
embryos
Cell killing in vitro HTO and chronic gamma rays 1.3 Ueno et al. (1989)

*H-amino acids and chronic
gamma rays 1.7

Tritiated thymidine @H-Tdr)’
and chronic gamma rays 3.5

“See Table 4 of Straume and Carsten (1993).
>Use of methy!“H-Tadr resulted in an identical RBE.

Taking into account the data on RBE relative to gamma rays and X rays, we describe the
REF for °H beta particles at low doses and low dose rates, REF,, by a lognormal probability
distribution having a 95% confidence interval between 1.2 and 5.0. This distribution has a
geometric mean (median) and geometric standard deviation of 2.4 and 1.4, respectively. Based
on discussions presented below and except as noted, the probability distribution of REF, for 7H
beta particles is assumed to apply to any electrons of energy less than 15 keV.

In a previous analysis by SENES Oak Ridge (Thomas and Hoffman, 2000), the biological
effectiveness of °H beta particles was described by a triangular probability distribution having a
lower bound of 1.0, a mode of 2.0, and an upper bound of 5.0. The lognormal probability
distribution described above is similar to the previous assumption. However, the data
summarized in Tables 13-16 indicate that an REF, greater than 5 cannot be ruled out. The upper
tail of the lognormal probability distribution represents an assumption that REF, could be 5 or
greater, and that a reasonable upper bound cannot be determined with certainty. The small
probability assigned to an REF, of 4 or greater (about 10%) also is intended to take into account
that RBEs for organically-bound tritium appear to be 2-3 times higher than RBEs for HTO or *H
incorporated into amino acids (see Tables 14 and 16). This is a potentially important
consideration when some HTO taken into the body becomes organically-bound before it is
excreted (Straume and Carsten, 1993).

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DRAFT June 17, 2002

exposure to *H beta particles are estimated using the models represented in eqs. (2) and (5),
which apply at low doses and low dose rates. If we assume that DDREF for *H beta particles in
the various studies is about the same as DDREF for the reference radiation, RBEs obtained under
conditions of chronic exposure in Tables 13-16 provide estimates of RBEy.

Based on the data under conditions of chronic or sub-acute exposure to gamma rays in
Tables 13-16, but excluding the data for tritiated thymidine, central estimates of RBE, are in the
range of about 1.5-3. When uncertainties in these estimates are considered, the range presumably
is about 1.2-4. The data on RBE for tritiated thymidine are not included based on the
consideration that this compound has a different distribution within the body than other chemical
forms of *H that would be encountered in the workplace or the environment.

Estimates of RBE,, under conditions of chronic exposure to X rays also are refevant. In
three of the five such determinations, the central estimate of RBE,, is about 2-3. If we assume a
nominal biological effectiveness of X rays relative to gamma rays of 2, based on the probability
distribution of REF, for X rays developed in the previous section, these data indicate that RBE,,
for 5H beta particles relative to gamma rays is as high as about 4-6.

Table 13. Estimates of RBE of tritium beta particles for carcinogenesis endpoints*

Radiation and

Effect conditions RBE Reference
Mammary tumors in HTO and chronic X rays 1.2+0.3  Gragtmans et al. (1984)
S-D rats
Leukemia in CBA/H HTO and chronic X rays 1.2+0.3 Myers and Johnson
mice (1991)

Tumors in CS7BI/6N x HTO and acute gamma ~P Yokoro et al. (1989)
C3H/He mice Tays

Transformation in HTO and acute X rays ~1 Suzuki et al. (1989)
hamster cells in vitro

Transformation in HTO and acute X rays 1-2 Little (1986)

mouse cells in vitro

Transformation in 10T’ HTO and subacute 1.4-1.8 Yamaguchi et al. (1985)
cells gamma rays

“See Table 1 of Straume and Carsten (1993),
» authors did not provide estimate of RBE but state that biological effectiveness of HTO and
gamma rays was not very different.

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DRAFT June 17, 2002

Table 12. Summary of probability distributions of radiation effectiveness factors for
photons to be used in estimating cancer risks and probability of
causation in accordance with eq. (11), (12), or (13)*

Photon energy Probability distribution of radiation effectiveness factor (REF,)
> 250 keV Single-valued at 1.0 (higher-energy photons are assumed reference
radiation)
30-250 keV Hybrid distribution with —

75% weight to lognormal distribution having a 95% confidence
interval between 1.0 and 5.0;
25% weight to value 1.0;

< 30 keV Product of two distributions —

(1) hybrid distribution for photons of energy 30-250 keV; and
(2) triangular distribution with minimum of 1.0, mode of 1.3,
and maximum of 1.6

“Probability distributions apply to all cancers and at any dose and dose rate.

ELECTRONS

With the exception of low-energy electrons emitted in beta decay of *H, there have been
few studies of the biological effectiveness of electrons relative to gamma rays or X rays. In this
section, we develop a probability distribution of an REF for beta particles emitted in *H decay;
these electrons have an average energy of 5.7 keV and a maximum energy of 18.6 keV (Kocher,
1981). We then consider the biological effectiveness of other electrons, including low-energy
Auger electrons.

REF for Tritium Beta Particles

Many studies have shown that beta particles emitted in decay of °H are biologically more
effective than gamma rays in inducing stochastic effects (NCRP, 1990; Straume and Carsten,
1993). Estimates of RBE obtained from studies reviewed by Straume and Carsten (1993),
including studies in which the reference radiation was X rays, are summarized in Tables 13-16.

For purposes of developing an REF for *H beta particles that is consistent with the REFs
for the other radiation types, the relevant studies are those in which the reference radiation was
gamma rays. In most studies using gamma rays, the reference radiation was delivered chronically
to match the conditions of exposure to 7H beta particles. Thus, cancer risks in humans from

51


DRAFT

June 17, 2002

Table 14. Estimates of RBE of tritium beta particles for genetic endpoints (continued)*

Effect

Radiation and
conditions

RBE Reference

Dominant lethals in male
mice

Dominant lethals in female

mice

Specific locus mutations in

male mice

HTO and chronic gamma
rays

HTO and chronic gamma
rays

HTO and chronic gamma
rays

2.5 Searle (1984)

1-2 Carsten and
Commerford (1976)

2.5 Xiang-yan et al.
(1986)

2.0 UNSCEAR (1982)

“See Table 2 of Straume and Carsten (1993).
Use of methyl-*H-Tdr resulted in identical RBEs.

Table 15. Estimates of RBE of tritium beta particles for chromosome

aberrations in human lymphocytes*

Radiation and conditions RBE Reference

HTO and acute X rays 1940.7 Bocian et al. (1977), as refit by
Prosser et al. (1983)

HTO and subacute gamma rays 1.49 +0.21 Morimoto et al. (1989)

HTO and acute X rays 1.13 £0.18 Prosser et al. (1983)

HTO and acute gamma rays 3.4+0.6 Prosser et al. (1983) and Lloyd et
al. (1975)

HTO and subacute X rays 2.6 Vulpis (1984)

HTO and low dose X rays 2.0 Estimated from Prosser et al.

(1983) and Lloyd et al. (1988)

“See Table 3 of Straume and Carsten (1993).

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DRAFT June 17, 2002

central estimates and 95% confidence intervals (in parentheses) of the excess relative risk (ERR)
of thyroid cancer per Gy in children have been reported:

* 4,7 (1.7, 11) - atomic-bomb survivors less than 15 years old at time of exposure, with a
mean thyroid dose of gamma rays of 0.27 Gy (Ron et al., 1995);

* 9,5 (4.1, 19) - atomic-bomb survivors less than 10 years old at time of exposure, with the
same mean thyroid dose (Thompson et al., 1994).

These estimates suggest that the risk to children of age less than 10 years at time of exposure is
greater than the risk to children of age 10-15 years. For children exposed to X rays, the following
estimates of the ERR of thyroid cancer per Gy have been reported (Ron et al., 1995):

* 9.1 (3.6, 29) — newborn children in Rochester, New York, treated for an enlarged thymus
gland at ages less than 1 year, with a mean thyroid dose of X rays of 1.4 Gy;

* 33 (14, 57) — Israeli children treated for ringworm of the scalp at a mean age of 7 years,
with a mean thyroid dose of X rays of 0.09 Gy;

* 2.5 (0.6, 26) — children in Chicago, Illinois, treated for enlarged tonsils and adenoids at
ages 0-15 years (mean age of 4 years), with a mean thyroid dose of X rays of 0.59 Gy;

* 7,7 (2.1, 29) — pooled analysis of data on childhood exposures at ages 0-15 years,
including data on the atomic-bomb survivors (result is dominated by data on childhood
exposures to X rays at ages less than 10 years).

An RBE for X rays can be estimated from these results by assuming that the probability
distribution of the estimated risk in each study is lognormal and calculating ratios of the
probability distributions for X rays to a distribution for gamma rays. Since the average ages of
children exposed to X rays were 7 years or less, we use the estimated risk in the atomic-bomb
survivors of age less than 10 years at time of exposure to estimate RBEs. The 95% confidence
intervals of RBEs obtained from the three studies of children exposed to X rays are (0.3, 4.2),
(1.1, 9.2), and (0.06, 3.5), and the 95% confidence interval obtained using the results of the
pooled analysis is (0.2, 4.0). If we assume that the biological effectiveness of X rays in humans
should not be less than that of high-energy gamma rays, based on the effective quality factor
shown in Fig. 1 (ICRU, 1986), these confidence intervals indicate that the RBE of X rays in
inducing thyroid cancer in children most likely is in the range of about 1-4. However, the
estimated risks in the different populations neither support nor refute an assumption that X rays
are more effective than high-energy gamma rays in inducing thyroid cancer in children.

Additional information on the RBE for X rays and thyroid cancer can be obtained from a
study of prepubescent rats exposed to X rays and beta particles emitted in "*'I decay (Lee et al.,
1982). As discussed in a later section, the biological effectiveness of 'I beta particles, which
have an average energy of 182 keV (Kocher, 1981), should be similar to that of high-energy
gamma rays. The following central estimates and 95% confidence intervals (in parentheses) of
ratios of thyroid tumor incidence from exposure to X rays to tumor incidence from exposure to
51] beta particles were obtained: 1.1 (0.32, 3.7) at a mean thyroid dose of 0.8 Gy, 1.2 (0.43, 3.2)

46


DRAFT June 17, 2002

The energies of secondary electrons produced by interactions of photons in tissue
generally decrease with decreasing photon energy. Therefore, electrons produced by interactions
of 250-keV photons in tissue are at the highest energies for which the biological effectiveness
should be the same as that of lower-energy photons. In tissue, which has an average atomic
number of 7 (Shleien et al., 1998), Compton scattering is the dominant interaction at a photon
energy of 250 keV [see Fig. A.1 of NCRP (1991) and Figs. 5.1 and 5,2 of Shleien et al. (1998)].
At this energy, the continuous spectrum of secondary electrons produced by Compton scattering
has a maximum energy of 124 keV and an average energy of 60 keV (Turner, 1995). In contrast,
the energy of secondary electrons produced by the photoelectric effect in tissue at this energy is
nearly 250 keV, since the binding energies of electrons in atoms of the elements comprising
tissue are about 3 keV or less (Shleien et al., 1998). At 250 keV, however, photoelectrons are
produced in only about 0.1% of all interactions [see Fig. 5.2 of Shleien et al. (1988)] and, thus,
have little effect on the average energy of secondary electrons.

As the incident photon energy decreases below 250 keV, the photoelectric effect increases
in importance relative to Compton scattering and becomes the dominant interaction in tissue at
energies less than about 30 keV (Schleien et al., 1998; NCRP, 1991). At this photon energy, the
average and maximum energies of secondary electrons produced in Compton scattering are about
1.5 and 3 keV, respectively, and the average energy of photoelectrons is nearly 30 keV. Thus,
the average energy of secondary electrons produced by 30-keV photons is about 15 keV, This
result is of interest because we have assumed, based on the calculated energy dependence of the
effective quality factor shown in Fig. 1, that the biological effectiveness of photons of energy less
than 30 keV is higher than at 30-250 keV. Thus, the same increase in biological effectiveness
should apply to electrons of energy less than about 15 keV. As the photon energy decreases
below 30 keV, the average energy of secondary electrons produced in tissue approaches the
incident photon energy, due to the increasing importance of the photoelectric effect and the low
binding energies of atomic electrons. At a photon energy of 20 keV, for example, the energies of
secondary electrons are little different from the incident photon energy.

Three conclusions can be drawn from the analysis described above. First, at energies
greater than about 60 keV, the biological effectiveness of electrons should be essentially the
same as that of the reference high-energy gamma rays (i.e., unity). Second, at energies in the
range of about 15-60 keV, the biological effectiveness of electrons should be the same as that of
photons of energy 30-250 keV. Third, at energies less than about 15 keV, but possibly excluding
Auger electrons as discussed below, the biological effectiveness of electrons should be the same
as that of photons of energy less than 30 keV.

We use the conclusions about the biological effectiveness of electrons of various energies
in the following way. First, the assumed probability distribution of REF, for beta particles from
3H decay is applied to any electrons of energy less than 15 keV. In general, this REF, should be
applied to electrons from beta decay when the average energy of the spectrum of beta particles is
less than 15 keV. Use of the average energy of beta particles is reasonable when the argument to
assume an REF, greater than 1.0 at energies less than 15 keV was based in part on the average

57


DRAFT June 17, 2002

In a recent analysis by Harrison et al. (2002) of the NRPB, the biological effectiveness of
5H beta particles relative to high-energy gamma rays was described by a uniform probability
distribution between 1.0 and 2.5; this distribution has a median of 1.75. The analysis by Harrison
et al. differs from the analysis in this report mainly in two respects. First, these investigators
evaluated RBEs for °H beta particles relative to high-energy gamma rays and RBEs relative to
lower-energy X rays together without taking into account that X rays probably have a greater
biological effectiveness than gamma rays. As discussed above, we have assumed that RBEs for
5H beta particles relative to X rays should be increased by a factor representing the biological
effectiveness of X rays to provide a proper comparison with RBEs relative to gamma rays. This
adjustment by a factor of about two results in a median and upper confidence limit in our
probability distribution of REF, that are substantially higher than assumed by Harrison et al.
Second, the uniform probability distribution developed by Harrison et al. incorporates an
assumption that the biological effectiveness of *H beta particles relative to gamma rays could not
exceed 2.5. In contrast, we believe that the data on RBE are consistent with values as high as
about 5, and that an upper bound near 5 cannot be established with certainty. These assumptions
are incorporated in the lognormal probability distribution of REF, developed in this report.

The assumed lognormal probability distribution of REF, for *H beta particles having a
95% confidence interval between 1.2 and 5.0 is nearly the same as the probability distribution of
REF, for photons of energy less than 30 keV discussed in the previous section. This consistency
is expected when, as discussed below, the energies of electrons that deliver an absorbed dose are
similar in the two cases.

Consideration of Energy Dependence of REF

Since the energies of °H beta particles are very low, we also considered whether other
electrons, especially those of higher energy, should have an REF greater than unity. In radiation
protection, all such electrons generally are assumed to have the same biological effectiveness as
high-energy gamma rays (see Table 1). A study of the biological effectiveness of X rays and beta
particles from '"'I decay in inducing thyroid cancer in rats by Lee et al. (1982) discussed
previously is the only study we are aware of that was designed to investigate the biological
effectiveness of higher-energy electrons. In the absence of extensive radiobiological data, we
address this question using the following arguments.

In the previous section, data on the biological effectiveness of X rays and a calculation of
the energy dependence of the effective quality factor for photons shown in Fig. 1 were used to
develop a probability distribution of REF, with a median greater than 1.0 for photons of energy
as high as 250 keV. Since the absorbed dose from irradiation by photons is due almost entirely
to energetic secondary electrons produced by interactions of the incident photons in tissue,
information on the biological effectiveness of photons can be used to infer the biological
effectiveness of electrons. That is, an REF for photons of a given energy essentially describes the
biological effectiveness of the secondary electrons produced by the first interactions of the
photons in tissue.

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DRAFT

June 17, 2002

Table 14. Estimates of RBE of tritium beta particles for genetic endpoints’

Radiation and

Effect conditions RBE Reference
6-Thioguanine resistance in HTO and chronic gamma 2.9 Ueno et al. (1989)
mouse cells in vitro rays
6-Thioguanine resistance in *H-amino acid and chronic 2.6 Ueno et al. (1989)
mouse cells in vitro gamma rays
6-Thioguanine resistance in _Tritiated thymidine (H-Tdr)’ 5.9 Uenoet al. (1989)
mouse cells in vitro and chronic gamma rays
6-Thioguanine resistance in HTO and gamma rays at 10° Nakamura et al.
mouse cells in vitro mutant frequency (1985)

acute 1.5
chronic 2.4
Chromosome aberrations in | HTO and chronic X rays 3 Kamiguchi et al.
human sperm in vitro (1990)
Chromosome aberrations in HTO and chronic gamma 1.9 Suyama and Etoh
fish lymphocytes in vitro rays (1985)
Chromosome aberrations in | HTO and chronic gamma 1.8 Matsuda et al.
mouse zygotes rays (1985)
Chromosome aberrations in Chopra and Heddle
CBA/H mice (1988)
lymphocytes HTO and X rays 1d
spermatogonia HTO and X rays 1.2
Micronuclei in mammalian HTO and chronic gamma 2.0 Ueno et al. (1982)
cells rays 2.7 Kashima et al.
(1985)
Mutations in Drosophila HTO and gamma rays 2.7 Byrne and Lee
spermatozoa (1989)
Mutations in mice in vivo HTO and chronic gamma 2.7 Nomura and
rays Yamamoto (1989)

Table is continued on following page.

53


DRAFT June 17, 2002

Prababili

0.00 1.25 2.50 3.75 5.00

Fig. 18. Assumed probability distribution of REF, for photons of energy 30-250 keV (25% weight to
value 1.0; 75% weight to lognormal probability distribution having a 95% confidence interval
between 1.0 and 5.0) displayed as a cumulative distribution; distribution applies to all cancers
and at any dose and dose rate. Median of distribution is 1.9, and 95% confidence interval lies
between 1.0 and 4.7; about 1.8% of values lie beyond 5.0.

.037;

024

Probabili

01

cy ll it,
0.50 2.00 3.50 5.00 6.50

Fig. 19, Assumed probability distribution of REF, for photons of energy less than 30 keV; distribution
applies to all cancers and at any dose and dose rate. Median of distribution is 2.4 and 95%
confidence interval lies between 1.1 and 6.1; about 1.8% of values lie beyond 6.5.

49


DRAFT June 17, 2002

Leukemias (chronic exposure) —

HR, = a x REF,, x D, (16)

where REF, , is the radiation effectiveness factor at low doses and low dose rates, R,., is the risk
coefficient (ERR per Gy) at high acute doses of high-energy gamma rays for the solid tumor of
concern, a and b are the coefficients of the linear and quadratic terms in the linear-quadratic
dose-response relationship for leukemias at high acute doses of high-energy gamma rays,
DDREF, is the dose and dose-rate effectiveness factor for gamma rays and other low-LET
radiations, and D, is the absorbed dose of electrons in the organ or tissue of concern. A
probability distribution of REF, based on RBEs for beta particles emitted in decay of *H is
applied at all electron energies less than 15 keV (i.e., when the average energy of beta particles or
the energy of discrete electrons is less than 15 keV), except the distribution does not apply when
an Auger-emitting radionuclide is known to be incorporated into DNA. The probability
distribution of REF, for low-energy electrons is applied to all cancers. The value of REF, for all
electrons of energy greater than 15 keV is assumed to be unity.

As described previously in the summary for photons, a single probability distribution of
DDREF, is applied in estimating risks of solid tumors under conditions of chronic exposure to
electrons, and DDREF, under conditions of acute exposure depends on the magnitude of the dose
(Land et al., 2002). Acute exposure to beta particles and other electrons emitted by radionuclides
is not expected to be of concern. For example, given the residence half-time of tritiated water in
soft tissues of about 10 days (ICRP, 1979) and the longer half-life of 5H (12.3 years), exposures
to beta particles emitted by °H generally should be chronic. Acute exposure to electrons
presumably is a concern only in situations involving unusual external exposures.

The assumed REF, for low-energy electrons would be important in calculating cancer
risks and probability of causation whenever intakes of radionuclides that emit low-energy beta
particles, internal conversion electrons, or Auger electrons contribute significantly to estimated
doses to an organ or tissue of concern, Examples of potentially important radionuclides include,
in addition to *H, the beta-emitting radionuclides 'Ru and '’Pd and the Auger-emitting
radionuclides *'Cr, “Fe, *7Co, “Co, “Zn, and '*I (Kocher, 1981).

Based on considerations of the energies of secondary electrons produced by interactions
of photons in tissue and the assumed REF, for photons of energy 30-250 keV, REF, also should
be greater than unity at electron energies of 15-60 keV. However, such an REF, is not adopted in
this work, due to the lack of supporting radiobiological data.

The assumed probability distributions of REF, for electrons of different energies are
summarized in Table 17.

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DRAFT June 17, 2002

effectiveness in humans as high-energy gamma rays. The resulting probability distribution of
REF, has a median of 1.9 and a 95% confidence interval between 1.0 and 4.7. The cumulative
probability distribution of REF, is shown in Fig. 18. The assumption that this distribution
applies at photon energies of 30-250 keV is discussed below.

The weight to be given to an assumption that X rays and other lower-energy photons have
the same biological effectiveness in humans as high-energy gamma rays clearly is a matter of
subjective judgment. Our judgment is that the weight given to this assumption should be
substantial but should not be much higher than 25% (e.g., 50% or higher). This judgment is
based on two considerations. First, there are many and varied radiobiological studies which
clearly indicate a greater biological effectiveness of X rays. Second, although the
epidemiological data do not show clear evidence of a difference in biological effectiveness, the
data are so uncertain that differences as large as a factor of 3 cannot be ruled out.

Energy Dependence of REF

Based on the energy dependence of the effective quality factor shown in Fig. 1 (CRU,
1986), we assume that the probability distribution of REF, for orthovoltage X rays and other
lower-energy photons described above applies at energies of 30-250 keV; the effective quality
factor is essentially independent of energy over much of this range. We also note that the
effective quality factor at these energies is approximately twice the value at the energies of Co
gamma rays; by our reading of the curve in Fig. 1, the difference is a factor of 2.3. The ICRU’s
calculation thus supports our assumed distribution of REF,.

An assumption that the distribution of REF, applies at photon energies as low as 30 keV
is supported by calculations of the biological effectiveness of 60- and 80-kVp X rays relative to
gamma rays from the Hiroshima and Nagasaki atomic bombs for a number of specific endpoints,
including chromosomal aberrations in human lymphocytes, induction of mutations in human
fibroblasts, and oncongenic transformation in C3H10TY% mouse cells (Brenner, 1999). RBEs at
low doses between 1.6 and 2.0 were calculated. The differences between these values and the
value of 2.3 inferred from the calculation in Fig. 1 are due, in part, to differences in the assumed
responses as a function of lineal energy and to an assumption that the average energies of gamma
rays from the atomic bombs were somewhat less than the energies of °Co gamma rays.

The effective quality factor shown in Fig. 1 also indicates that the biological effectiveness
of photons increases as the energy decreases below 30 keV. For example, based on the
calculation in Fig. 1, Brenner and Amols (1989) estimated that 23 kVp X rays should be
approximately 1.3 times more effective than 44-250 kVp X rays in inducing breast cancer. Thus,
we assume that the probability distribution of REF, for photons of energy 30-250 keV should be
increased when the energy is less than 30 keV. We represent this increase by a factor which is
described by a triangular probability distribution having a lower bound of 1.0, a mode of 1.3, and
an upper bound of 1.6. The resulting probability distribution of REF, at photon energies less
than 30 keV is shown in Fig. 19.

48


DRAFT June 17, 2002

at 3.3 Gy, and 1.4 (0.24, 7.6) at 8.5 Gy. The average of the three confidence intervals is a
distribution with a central estimate (50" percentile) and 95% confidence interval of 1.4 (0.6, 3.6).
Thus, although the uncertainties are large and an RBE for X rays as high as about 4 cannot be
ruled out, the biological effectiveness of X rays and ‘I beta particles in inducing thyroid cancer
in the study animals was about the same, on average.

Finally, we examined results obtained from epidemiological studies of cancers at other
sites, including the colon, lung, skin, female breast, and bladder (UNSCEAR, 2000). The central}
estimate of the ERR per Gy in populations exposed to X rays often was comparable to or less
than the central estimate in a similar age group in the atomic-bomb survivors, although some of
the lower risks from X rays may be influenced by the much higher doses of X rays compared with
the doses of gamma rays in the atomic-bomb survivors. In those few cases where a higher risk
was observed in populations exposed to X rays, the difference was less than a factor of 2. In all
cases, however, uncertainties in the risk estimates are sufficiently large that an RBE for X rays
substantially greater than 1 cannot be ruled out. Thus, as in the case of thyroid cancer, the
available data on other cancers in humans do not indicate whether X rays are biologically more
effective than high-energy gamma rays or not.

The results of epidemiological studies described above lead to the following observations.
First, there is no evident difference in the effectiveness of X rays in inducing thyroid cancers
compared with cancers at other sites. Second, uncertainties in the results of epidemiological
studies are sufficiently large that an upper confidence limit of REF, as high as 5.0, as we have
assumed based on radiobiological data, cannot be ruled out. Third, although uncertainties in the
results of epidemiological studies are large, in no cases is a central estimate of an RBE for X rays
as high as 4 obtained. Based on considerations of statistical uncertainties alone, an occasional
high estimate of RBE would be expected. Finally, the epidemiological data do not rule out an
assumption that the biological effectiveness X rays in inducing cancers in humans is the same as
that of high-energy gamma rays.

Based on the evidence obtained from all the radiobiological and epidemiological studies
discussed above and an assumption that the biological effectiveness of X rays should not be
substantially jess than that of high-energy gamma rays, we describe REF, for orthovoltage X rays
and other lower-energy photons by the following hydrid probability distribution:

1) 75% weight to a lognormal distribution having a 95% confidence interval between
1.0 and 5.0, based on the results of radiobiological studies;

{2] 25% weight to the value 1.0, based on the lack of clear evidence of a difference
between X rays and gamma rays in epidemiological data.

Thus, we use the results of epidemiological studies to modify the lognormal probability

distribution that was based on the results of radiobiological studies by assigning a substantial
weight to an assumption that X rays and other lower-energy photons have the same biological

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DRAFT June 17, 2002

energy of the spectrum of secondary electrons in Compton scattering. The assumed REF, also
should be applied to discrete internal conversion electrons of energy less than [5 keV emitted in
radioactive decay.”' In these cases, however, an increased biological effectiveness needs to be
taken into account only when the average energy of low-energy internal conversion electrons per
decay of a radionuclide is significant compared with the average energies per decay of other
radiations that have a short range in tissue, including internal conversion electrons of energy
greater than 15 keV, beta particles, and alpha particles. Application of the assumed REF, to
Auger electrons is discussed below.

Second, we have not adopted an increased biological effectiveness of 15-60 keV electrons
relative to high-energy photons, even though the calculations described above indicate that REF,
for electrons in this energy range should be the same as that for 30-250 keV photons. This
decision was based on two considerations noted previously. First, we are not aware of any data
on RBE for 15-60 keV electrons. Second, the assumed REF, for 30-250 keV photons is based on
studies in which the average energies of X rays was about 50-65 keV and relatively few X rays
had energies above 100 keV, and the assumption that RBEs for such X rays apply at photon
energies up to 250 keV was based on a calculation of the energy dependence of the effective
quality factor shown in Fig. 1. Thus, adoption of an REF, greater than unity for 15-60 keV
electrons would be based on two assumptions for which there is no experimental evidence. In
general, we have assumed that probability distributions of REFs should be developed only when
there is some basis in radiobiological data.

Biological Effectiveness of Auger Electrons

Radionuclides that emit Auger electronsTM require special consideration, due to the very
low energies of these radiations (often a few keV or less) and their short range in matter (less
than 0.1 pm). The ICRP (1991) and the NCRP (1993) recommend that Auger electrons emitted
by radionuclides that are incorporated into DNA should not be assigned a radiation weighting
factor of 1 (see Table 1), since it is unreasonable to average the absorbed dose over the whole
mass of DNA. Techniques of microdosimetry are considered more appropriate in such cases.

2\nternal conversion is the process by which the energy difference between an initial and final
state in an atomic nucleus is transferred directly to a bound atomic electron, which is then ejected from
the atom (NCRP, 1985), Emission of internal conversion electrons competes with emission of gamma
rays, and it increases in importance as the atomic number increases and the transition energy decreases.

2The emission of Auger electrons competes with the emission of X rays as a means of carrying
off the energy released when a vacancy in an inner atomic shell of electrons, created by an electron
capture or internal conversion electron event, is filled by an electron from an outer shell (NCRP, 1985).
In the Auger process, the filling of a vacant inner shell is accompanied by the simultaneous ejection of
one or more electrons from an outer shell. Auger electrons are important compared with other radiations
having a short range in matter (beta particles, internal conversion electrons, and alpha particles) mainly
when a radionuclide decays by electron capture or an isomeric transition (Kocher, 1981).

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